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Anti-tumor antibody compositions and methods of use

a technology of anti-tumor antibodies and compositions, applied in the field of anti-tumor antibody compositions and methods, can solve the problems of widespread use of psa as a screening tool, disease progression and death, and very limited treatment options for advanced diseases

Inactive Publication Date: 2008-10-14
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0018]In a further aspect, the invention provides an article of manufacture comprising a container and a composition contained therein, wherein the composition comprises an anti-PSCA antibody

Problems solved by technology

Patients with metastatic prostate cancer on hormonal therapy will eventually develop an androgen-refractory (androgen independent) state that will lead to disease progression and death.
However, widespread use of PSA as a tool for screening is controversial since PSA fails to discriminate accurately between benign and malignant prostate disease.
While surgical or radiation therapy significantly improves survival in patients with early stages of the disease, the therapeutic options are very limited for advanced cases, particularly for tumor recurrences following hormone ablation.
Currently, there is no effective treatment for the 20-40% of prostate cancer patients who develop recurrent disease after surgery or radiation therapy, or for those in whom the cancer has metastasized at the time of diagnosis.
Chemotherapy has its toxic side effects, especially in elderly patients.

Method used

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  • Anti-tumor antibody compositions and methods of use
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  • Anti-tumor antibody compositions and methods of use

Examples

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experimental examples

VIII. EXPERIMENTAL EXAMPLES

[0280]The above and other features of the invention will now be described more particularly with reference to the accompanying figures and pointed out in the claims. The particular embodiments described below are provided by way of illustration and are not meant to be construed as a limitation on the scope of the invention. It will be apparent to one of ordinary skill in the art that many modifications can be made to the present invention without departing from the spirit or essential characteristics of the invention.

example 1

[0281]The preparation and characterization of the anti-PSCA monoclonal antibodies are described.

I. Materials and Methods

[0282]Hybridomas producing murine and human anti-PSCA monoclonal antibodies (Mabs) were generated. The fusion partner was the mouse myeloma line P3X63Ag8.653 (Kearney, J. F. et al., J. Immunology 123:1548-1550, 1979).

[0283]Table 2A summarizes the immunization strategies and shows the nature of the antigen used for immunization, the adjuvant, dosage, route of administration, dosing schedule and host animal used. Table 2B summarizes the characteristics of the anti-PSCA Mabs as determined by various assays. The antibody names herein are derived from the first 3-4 characters of the hybridoma clone producing the antibody (see Table 2B). The first 3-4 characters before the period in the clone name indicate the parental clone followed after the first period by the name of further subclones, if any. Alternatively, the anti-PSCA antibodies herein are also referred to by the...

example 2

[0307]This example demonstrated the binding and localization of anti-PSCA antibodies 2395 (6F8), 2399 (8D11), 2403 (5F2), 2761 (6B8) [ascites number followed by antibody no. in parenthesis; see Table 2B] to PSCA expressing tumor cells (MCF-7Her2gdPSCA and HCT-gdPSCA) in vivo. By labeling antibodies with the fluorescent dye, Cy3, antibody binding can be visualized by fluorescence microscopy. This technology was well established using Cy3 labeled Herceptin (anti-Her2 monoclonal antibody) in mice bearing Her2-expressing tumors. In vivo binding of the anti-PSCA antibodies were tested on tumor cells transfected with human gd-linked PSCA. Control antibodies included Cy3 labeled Herceptin as a positive control for the MCF-7Her2gdPSCA cells. Additionally, a Cy3 labeled anti-gd antibody, with very good binding activity, was used as a positive control for the PSCA antibodies. Transfected PSCA is gd linked, thus the level of gd protein directly correlates with PSCA protein expression. Cell lin...

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Abstract

The invention provides antibodies targeted at a tumor antigen prevalent on prostate tumors and methods useful in alleviating cancers expressing the antigen, as well as nucleic acids and cells for expressing the antibodies.

Description

RELATED APPLICATIONS[0001]This application is a divisional application of U.S. patent application Ser. No. 09 / 698,705 now U.S. Pat. No. 6,824,780, filed on Oct. 27, 2000, which claims the benefit under 35 U.S.C. §1.19(e) to provisional application 60 / 162,558 filed Oct. 29, 1999, and 60 / 182,872 filed Feb. 16, 2000, the entire disclosures of which are hereby incorporated by reference.FIELD OF THE INVENTION[0002]The present invention relates to anti-PSCA antibody compositions and methods of killing PSCA-expressing cancers cells.BACKGROUND OF THE INVENTION[0003]In humans, prostate cancer is one of the most commonly diagnosed malignancies in males and is the second leading cause of cancer related death in men. The American Cancer Society estimates that for the year 2000, 180,400 new cases of prostate cancer will be diagnosed with 31,900 deaths from the disease. In advanced stages, prostate cancer metastasizes to the bone. While advances in early diagnosis and treatment of locally confine...

Claims

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Application Information

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IPC IPC(8): A61K39/395C07K14/47C07K14/705C07K16/18
CPCC07K14/4748C07K14/705C07K16/18C07K2317/21C07K2317/24C07K2317/34C07K2317/77C07K2319/00
Inventor DEVAUX, BRIGITTEKELLER, GILBERT-ANDREKOEPPEN, HARTMUTLASKY, LAWRENCE A.
Owner GENENTECH INC
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